PHYSIOLOGY OF THE MENSTRUAL CYCLE

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PHYSIOLOGY OF THE MENSTRUAL CYCLE

• Quoted with modification from Dr Salwa Neyazi
• King Saud University

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NORMAL MENSTRUAL CYCLE

• What is the mean duration of the MC?
• Mean 28 days (only 15 of ?)
• Range 21-35
• What is the average duration of menses?
• 3-8 days
• What is the normal estimated blood loss?
• Approximately 30 ml
• When does ovulation occur?
• Usually day 14
• 36 hrs after the onset of mid-cycle LH surge

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NORMAL MENSTRUAL CYCLE

• What regulates the phases of the MC ovulation?
• Interaction between hypothalamus, pituitary
  ovaries
• What is the mean age of menarche menopause?
• Menarche 12.7
• Menopause 51.4

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HYPOTHALAMIC- PITUITARY- OVARIAN AXIS
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PHASES OF THE MENSTRUAL CYCLE

• Ovulation divides the MC into two phases
• 1-FOLLICULAR PHASE
• -Begins with menses on day 1 ends with
  ovulation.
• ?RECRUITMENT
• FSH ? maturation of a cohort of
  ovarian
• follicles recruitment
• ? only one reaches maturity

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FOLLICULAR PHASE

• MATURATION OF THE FOLLICLE (FOLLICULOGENESIS)
• ? FSH ? primordial follicle
• (oocyte arrested in the diplotene stage of
  the 1st meiotic division surrounded by a single
  layer of granulosa cells)
• ? ? 1ry follicle
• (oocyte surrounded by a single layer of
  granulosa cells basement membrane thica cells)
• ? ? 2ry follicle or preantral follicle
• (oocyte surrounded by zona pellucida ,
  several layers of granulosa cells thica cells)
  

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FOLLICULOGENESIS (2)

• ?? tertiary or antral follicle
• 2ry follicle accumulate fluid in a
  cavity antrum.
• The oocyte is in eccentric position
• surrounded by granulosa cells
  cumulous oophorus

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FOLLICULOGENESIS (2)

• SELECTION
• ?Selection of the dominant follicle
  occurs days 5-7
• ?It depends on-
• - The intrinsic capacity
  of the follicle to
• synthesize estrogen
• -High est./and. ratio in
  the follicular fluid
• ?As the follicle matures ? ?
  estrogen ? ?FSH
• -ve feed back on the pituitary ?
  ?the follicle
• with the highest No. of FSH
  receptors will
• continue to thrive
• ? The other follicles that were
  recruited will
• become atretic

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• ? FSH ACTIONS
• -Recruitement
• -Mitogenic effect ? ? No. of granulosa
  cells
• ? FSH
  receptor
• -Stimulates aromatase activity ?
  conversion of
• androgens ? estrogens estrone
  estradiol
• - ? LH receptors
• ? ESTROGEN
• Acts synergistically with FSH to
• - induce LH
  receptors
• - induce FSH
  receptors in granulosa
• thica cells
• ? LH ? thica cells ? uptake of cholesterol
  LDL ?
• androstenedione testosterone

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FOLLICULOGENESIS (3)

• OTHER FACTORS THAT PLAY A ROLE IN
  FOLLICULOGENISIS
• -INHIBIN
• Local peptide in the follicular fluid
• -ve feed back on pituitary FSH secretion
• Locally enhances LH-induced androstenedione
  production

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FOLLICULOGENESIS (3)

• -ACTIVIN
• Found in follicular fluid
• Stimulates FSH induced estrogen production
• ? gonadotropin receptors
• ?androgen
• No real stimulation of FSH secretion in vivo
  (bound to protein in serum)
  

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PREOVULATORY PERIOD

• ? NEGATIVE FEEDBACK ON THE PIUITARY
• -? estradiol inhibin ?-ve feed back on
  pituitary ?
• ? FSH
• -This mechanism operating since childhood
• ? POSITIVE FEEDBACK ON THE PITUITARY
• ? ? estradiol (reaching a threshold
  concentration) ? ? ve feed back on the pituitary
  (facilitated by low levels of progestrone) ? ?
  LH surge ? secretion of progestrone
• Operates after puberty
• ve feed back on pituitary ? ? FSH

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PREOVULATORY PERIOD

• LH SURGE
• Lasts for 48 hrs
• Ovulation occurs after 36 hrs
• Accompanied by rapid fall in estradiol level
• Triggers the resumption of meiosis
• Affects follicular wall ? follicular rupture
• Granulosa cells ? lutenization ? progestrone
  synthesis

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OVULATION

• The dominant follicle protrudes from the ovarian
  cortex
• Gentle release of the oocyte surrounded by the
  cumulus
• granulosa cells
• Mechanism of follicular rupture
• 1-? Follicular pressure
• Changes in composition of the antral fluid ?
  ? colloid
• osmotic pressure

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OVULATION

• 2-Enzymatic rupture of the follicular wall
• LH FSH ? granulosa cells ? production of
  plasminogen activator
• ? ? plasmin ? ? fibrinolytic activity ? break
  down of follicular wall
• LH ? ? prostglandin E ? ? plasminogen
  activator
• ? ? PG F2a ? ? lysosomes under
  follicular wall

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LUTEAL PHASE

• LASTS 14 days
• FORMATION OF THE CORPUS LUTEUM
• After ovulation the point of rupture in the
  follicular wall seals
• Vascular capillaries cross the basement membrane
  grow into the granulosa cells ?? availability
  of LDL-cholesterol
• LH ?? LDL binding to receptors
• ?? 3a OH steroid dehydrogenase activity
• ?? progesterone

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LUTEAL PHASE

• Marked ? in progesterone secretion
• Progesterone actions
• -Suppresses follicular
  maturation on the
• ipsilateral ovary
• -Thermogenic activity ??
  basal body temp
• -Endometrial maturation
• Progesterone peak 8 days after ovulation (D22 MC)
• Corpus luteum is sustained by LH
• It looses its sensitivity to gonadotropins ?
  luteolysis ?
• ? estrogen progesterone level ?
  desquamation of the endometrium menses

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LUTEAL PHASE

• ?estrogen progestrone ? ? FSH LH
• The new cycle starts with the beginning of menses
• If pregnancy occurs ? hCG secretion ? maintains
  the
• corpus luteum

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ENDOMETRIAL CHANGES DURING THE MENSTRUAL CYCLE

• 1-Basal layer of the endometrium
• -Adjacent to the myometrium
• -Unresponsive to hormonal
  stimulation
• -Remains intact throughout the
  menstrual cycle
• 2-Functional layer of the endometrium
• Composed of two layers
• -Zona
  compacta ? superficial
  
• -Spongiosum
  layer

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ENDOMETRIAL CHANGES DURING THE MENSTRUAL CYCLE

• 1-Follicular /proliferative phase
• Estrogen ? mitotic activity in the glands
  stroma ?
• ? endometrial thickness from
  2 to 8 mm
• 2-Luteal /secretory phase
• Progesterone ?- Mitotic activity is severely
  restricted
• -Endometrial glands
  produce then secrete
• glycogen rich vacuoles
• -Stromal edema
• -Stromal cells
  enlargement
• -Spiral arterioles
  develop, lengthen coil

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MENSTRUATION

• Periodic desquamation of the endometrium
• The external hallmark of the menstrual cycle
• Just before menses the endometrium is infiltrated
  with leucocytes
• Prostaglandins are maximal in the endometrium
  just before menses
• Prostaglandins ? constriction of the spiral
  arterioles ?ischemia desquamation
• Followed by arteriolar relaxation, bleeding
  tissue breakdown

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HYPOTHALAMIC ROLE IN THE MENSTRUAL CYCLE

• The hypothalamus secretes GnRH in a pulsatile
  fashion
• GnRH activity is first evident at puberty
• Follicular phase GnRH pulses occur hourly
• Luteal phase GnRH pulses occur every 90 minutes
• Loss of pulsatility ?down regulation of pituitary
  receptors ? ? secretion of gonadotropins
• Release of GnRH is modulated by ve feedback by
• steroids
• gonadotropins
• Release of GnRH is modulated by external neural
  signals